Bibliographic Details
| Title: |
Exploitation of CD3ζ to enhance TCR expression levels and antigen-specific T cell function |
| Authors: |
Abdullah Degirmencay, Sharyn Thomas, Angelika Holler, Samuel Burgess, Emma C. Morris, Hans J. Stauss |
| Source: |
Frontiers in Immunology, Vol 15 (2024) |
| Publisher Information: |
Frontiers Media S.A., 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
TCR (T-cell receptor), TCR-T therapy, CD3-zeta, T cell function, TCR mispairing, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
The expression levels of TCRs on the surface of human T cells define the avidity of TCR-HLA/peptide interactions. In this study, we have explored which components of the TCR-CD3 complex are involved in determining the surface expression levels of TCRs in primary human T cells. The results show that there is a surplus of endogenous TCR α/β chains that can be mobilised by providing T cells with additional CD3γ,δ,ε,ζ chains, which leads to a 5-fold increase in TCR α/β surface expression. The analysis of individual CD3 chains revealed that provision of additional ζ chain alone was sufficient to achieve a 3-fold increase in endogenous TCR expression. Similarly, CD3ζ also limits the expression levels of exogenous TCRs transduced into primary human T cells. Interestingly, transduction with TCR plus CD3ζ not only increased surface expression of the introduced TCR, but it also reduced mispairing with endogenous TCR chains, resulting in improved antigen-specific function. TCR reconstitution experiments in HEK293T cells that do not express endogenous TCR or CD3 showed that TCRα/β and all four CD3 chains were required for optimal surface expression, while in the absence of CD3ζ the TCR expression was reduced by 50%. Together, the data show that CD3ζ is a key regulator of TCR expression levels in human T cells, and that gene transfer of exogenous TCR plus CD3ζ improved TCR surface expression, reduced TCR mispairing and increased antigen-specific function. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2024.1386132/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2024.1386132 |
| Access URL: |
https://doaj.org/article/8025343ede7741d989be0574485bfd42 |
| Accession Number: |
edsdoj.8025343ede7741d989be0574485bfd42 |
| Database: |
Directory of Open Access Journals |
